Coexistence of c-rmpA with p-rmpA and p-rmpA2 rather than excessive siderophores confers higher virulence in K1 Klebsiella pneumoniae.

Pyogenic liver abscess (PLA), which is particularly endemic in East Asia, is a relatively common and fatal infectious disease. Over the last 30-40 years, Klebsiella pneumoniae has replaced Escherichia coli as the dominant and overwhelming pathogen. To investigate the survival advantage of serotype K1 K. pneumoniae, we determined sequence types (STs), serotypes, and 11 virulence genes (allS, entB, irp2, iroN, iucA, fimH, mrkD, p-rmpA2, c-rmpA, p-rmpA, and peg-344). Virulence genes c-rmpA, p-rmpA, and p-rmpA2 in K. pneumoniae NTUH-K2044, which all confer hypercapsule and consequent hypervirulence, were deleted individually, and the consequent effects were evaluated. The lethality of various K1 K. pneumoniae strains was compared by using the Galleria mellonella model. In total, 31 K1 K. pneumoniae strains causing PLA and 30 causing non-PLA were identified. A significantly higher rate of c-rmpA was presented in PLA-derived K. pneumoniae strains than in non-PLA-derived strains. Similar ST23 (which dominates K1 strains) and string test-positive rates were observed in the two groups. Deletion of c-rmpA, p-rmpA, and p-rmpA2 individually did not confer significant effects on morphologies, such as positive string test, hypercapsule, and growth speed. Δc-rmpA presented weaker expressions of p-rmpA/p-rmpA2 than NTUH-K2044 and showed a higher expression of manC than Δp-rmpA and Δp-rmpA2. Three rmpAs conferred more virulence than one or two rmpAs, which presented an equally lethal effect in K1 K. pneumoniae. Klebsiella pneumoniae strains (H19 and H34) with the same genetic backgrounds except for siderophores showed equal virulence, but were less virulent than strain NTUH-K2044. Thus, the coexistence of c-rmpA with p-rmpA and p-rmpA2 enhances the lethality of K1 K. pneumoniae strains and the development of PLA. Excessive siderophores are not vital for the hypervirulence of K1 K. pneumoniae strains, although K1 strains usually harbour them on a molecular basis.

Prevalence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae under divergent evolutionary patterns.

K1/K2 hvKP strains acquire carbapenem-resistance plasmids, known as CR-hvKp, and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains obtain virulence plasmids, recognized as hv-CRKP. The two different evolution patterns of hypervirulent combined carbapenem-resistant Klebsiella pneumoniae may lead to their different prevalence in hospitals. Our study aimed to investigate the prevalence of hv-CRKP and CR-hvKp strains and to analyze factors influencing their evolution and prevalence. We collected 890 K. pneumoniae genomes from GenBank and 530 clinical K. pneumoniae isolates from nine hospitals. Our study found that hv-CRKP strains were more prevalent than CR-hvKp strains and both were dominated by blaKPC-2 gene. The blaKPC-2-carrying plasmids could mobilize non-conjugative virulence plasmids from hvKp strains to CRKP strains. The conserved oriT of virulence plasmids and the widespread of conjugative helper plasmids were potential factors for the mobilization of non-conjugative virulence plasmids. HvKp strains with KPC plasmid could hardly simultaneously exhibit hypervirulence and carbapenem resistance as CRKP strains with virulence plasmid, and we found that rfaH mutation reduced capsular synthesis and increased carbapenem resistance of the CR-hvKp strain. In summary, this study revealed that hv-CRKP strains were more suitable for survival in hospital settings than CR-hvKp strains and the widespread conjugative KPC-producing plasmids contributed to the emergence and prevalence of hv-CRKP strains.

Thermotherapy for knee osteoarthritis: A protocol for systematic review.

BACKGROUND: Osteoarthritis of the knee is one of the leading causes of pain and disability among adults. Thermotherapy has been widely used to treat knee osteoarthritis. But its efficiency has not been scientifically and methodically evaluated. The aim of this study is to assess the benefits of thermotherapy for people with osteoarthritis of the knee, in terms of pain, stiffness, and physical dysfunction. METHODS: Eight databases will be searched from their inception to September 2020. They are as follows: PubMed, Embase, Cochrane Library, ClinicalTrials.gov, China Knowledge Resource Integrated Database (CNKI), Weipu Database for Chinese Technical Periodicals (VIP), Chinese Biomedical Literature Database (CBM), and Wanfang Database. Two researchers will independently select studies, collect data, and assess the methodology quality by the Cochrane risk of bias tool. RESULTS: The systematic review will provide high-quality evidence to assess the benefits and harms of thermotherapy for people with osteoarthritis of the knee, in terms of pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events. CONCLUSION: The systematic review will provide evidence to assess the effectiveness and safety of thermotherapy for knee osteoarthritis patients. INPLASY REGISTRATION NUMBER: INPLASY202140038.